Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Urmia University of Medical Sciences, Urmia, Iran.
Department of Toxicology, Faculty of Pharmacy, Islamic Azad University, Shahreza, Iran.
Asian Pac J Cancer Prev. 2020 Jun 1;21(6):1773-1778. doi: 10.31557/APJCP.2020.21.6.1773.
Breast cancer is one of the most prevalent malignancies and leading causes of females' mortality worldwide. Because of resistance to various treatment options, new treatments based on molecular targeting has introduced as noticeable strategies in cancer treatment. In this regard, heat shock protein 90 (Hsp90) inhibitors are proposed as effective anticancer drugs. The goal of the study was to utilize a combination of the doxorubicin (DOX) and NVP-AUY 922 on the MCF-7 breast cancer model to investigate the possible cytotoxic mechanisms.
MCF-7 breast cancer cell line was prepared and treated with various concentrations of DOX and NVP-AUY922 in single-drug treatments. We investigated the growth-inhibitory pattern by MTT assay after continuous exposure to NVP-AUY922 and DOX in order to determine dose-response. Then the combinatorial effects were evaluated in concentrations of 0.5 × IC50, 0.2 × IC50, 1 × IC50 and, 2 × IC50 of each drugs. Based on MTT results of double combinations, low effective doses were selected for Real-time PCR [caspase3 and vascular endothelial growth factor(VEGF)] and caspase 3 enzyme activity.
A dose-dependent inhibitory effects were presented with increasing the doses of both drugs in single treatments. The upregulation of caspase 3 and downregulation of VEGF mRNA were observed in double combinations of NVP-AUY922 and DOX versus single treatments. Also, in these combinations in low doses of examined drugs (0.5 × IC50, 0.2 × IC50), higher caspase 3 activity were presented in comparison to single treatments (p<0.05).
Our findings indicate an effective action of NVP-AUY922 in combined with DOX in this cell line. These results can predict the treatment outcome in this model.
乳腺癌是全球最常见的恶性肿瘤之一，也是女性死亡的主要原因。由于对各种治疗选择的耐药性，基于分子靶向的新治疗方法已成为癌症治疗的显著策略。在这方面，热休克蛋白 90（Hsp90）抑制剂被提议作为有效的抗癌药物。本研究的目的是利用多柔比星（DOX）和 NVP-AUY922 的联合作用，在 MCF-7 乳腺癌模型中研究可能的细胞毒性机制。
制备 MCF-7 乳腺癌细胞系，并分别用不同浓度的 DOX 和 NVP-AUY922 进行单药处理。我们通过 MTT 法检测 NVP-AUY922 和 DOX 连续暴露后的生长抑制模式，以确定剂量反应。然后，在每种药物的 0.5×IC50、0.2×IC50、1×IC50 和 2×IC50 浓度下评估联合作用。基于 MTT 结果，选择低有效剂量进行实时 PCR[caspase3 和血管内皮生长因子（VEGF）]和 caspase 3 酶活性检测。
在单药治疗中，随着两种药物剂量的增加，呈现出剂量依赖性的抑制作用。与单药治疗相比，NVP-AUY922 和 DOX 的双重组合上调了 caspase 3，下调了 VEGF mRNA。此外，在这些组合中，在检查药物的低剂量（0.5×IC50、0.2×IC50）下，caspase 3 活性高于单药治疗（p<0.05）。
我们的研究结果表明，NVP-AUY922 与 DOX 联合在该细胞系中具有有效的作用。这些结果可以预测该模型的治疗结果。
